Abstract

A growing body of research has identified the mislocalization of TDP-43—a protein essential for regulating gene expression—as a hallmark of neurodegenerative disorders such as amyotrophic lateral sclerosis, frontotemporal lobar degeneration, Alzheimer’s disease, Lewy body dementia, and Huntington’s disease. While previous studies have largely focused on the nuclear roles of full-length TDP-43, a recent study by Deng et al. (2025) investigates the lesser-known consequences of its truncated forms in the cytoplasm, particularly their interactions with ribosomes—the cellular machinery that synthesizes proteins.